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issn:1532-429
1.  Arterial spin labeling perfusion cardiovascular magnetic resonance of the calf in peripheral arterial disease: cuff occlusion hyperemia vs exercise 
Background
Assessment of calf muscle perfusion requires a physiological challenge. Exercise and cuff-occlusion hyperemia are commonly used methods, but it has been unclear if one is superior to the other. We hypothesized that post-occlusion calf muscle perfusion (Cuff) with pulsed arterial spin labeling (PASL) cardiovascular magnetic resonance (CMR) at 3 Tesla (T) would yield greater perfusion and improved reproducibility compared to exercise hyperemia in studies of peripheral arterial disease (PAD).
Methods
Exercise and Cuff cohorts were independently recruited. PAD patients had an ankle brachial index (ABI) between 0.4-0.9. Controls (NL) had no risk factors and ABI 0.9-1.4. Subjects exercised until exhaustion (15 NL-Ex, 15 PAD-Ex) or had a thigh cuff inflated for 5 minutes (12 NL-Cuff, 11 PAD-Cuff). Peak exercise and average cuff (Cuffmean) perfusion were compared. Six participants underwent both cuff and exercise testing. Reproducibility was tested in 8 Cuff subjects (5 NL, 3 PAD).
Results
Controls had greater perfusion than PAD independent of stressor (NL-Ex 74 ± 21 vs. PAD-Ex 43 ± 10, p = 0.01; NL-Cuffmean 109 ± 39 vs. PAD-Cuffmean 34 ± 17 ml/min-100 g, p < 0.001). However, there was no difference between exercise and Cuffmean perfusion within groups (p > 0.6). Results were similar when the same subjects had the 2 stressors performed. Cuffmean had superior reproducibility (Cuffmean ICC 0.98 vs. Exercise ICC 0.87) and area under the receiver operating characteristic curve (Cuffmean 0.992 vs. Exercise 0.905).
Conclusions
Cuff hyperemia differentiates PAD patients from controls, as does exercise stress. Cuffmean and exercise calf perfusion values are similar. Cuff occlusion hyperemia has superior reproducibility and thus may be the preferred stressor.
doi:10.1186/s12968-015-0128-y
PMCID: PMC4336689
Peripheral arterial disease; Cardiovascular magnetic resonance; Perfusion; Arterial spin labeling; Cuff occlusion hyperemia
2.  A disproportionate contribution of papillary muscles and trabeculations to total left ventricular mass makes choice of cardiovascular magnetic resonance analysis technique critical in Fabry disease 
Background
Sphingolipid deposition in Fabry disease causes left ventricular (LV) hypertrophy, of which the accurate assessment is essential. Cardiovascular magnetic resonance (CMR) has been proposed as the gold standard. However, there is debate in the literature as to whether papillary muscles and trabeculations (P&T) should be included in LV mass (LVM).
Methods/results
We examined the accuracy of 2 CMR methods of assessing LVM and LV volumes, including (MincP&T) or excluding (MexP&T) P&T, in a cohort of Fabry disease subjects (n = 20) compared to a matched control group (n = 20). Significant differences between the two measurement methods were observed for LV end-diastolic volume, LV end-systolic volume, LVM, and LV ejection fraction (LVEF) in both groups. These differences were significantly greater in the Fabry group compared to controls, except for LVEF. P&T contributed to a greater percentage of LVM in Fabry subjects than controls (20 ± 1% vs 13 ± 2%, p = 0.01). In the control group, both volume-derived methods (MincP&T or MexP&T) provided accurate SV measurements compared with the internal reference of velocity-encoded aortic flow. In the Fabry group, inclusion of P&T (MincP&T) resulted in good concordance with phase contrast flow imaging (difference between flow and volume techniques: 1 ± 3 ml, p = 0.7).
Conclusion
The volumetric contribution of P&T in Fabry disease is markedly increased relative to healthy controls. Failure to account for this results in significant underestimation of LVM and results in misclassification of a proportion of subjects.
doi:10.1186/s12968-015-0114-4
PMCID: PMC4335368
Fabry disease; Papillary muscles; Left ventricular hypertrophy; Cardiovascular magnetic resonance imaging
3.  Characterization and quantification of dynamic eccentric regurgitation of the left atrioventricular valve after atrioventricular septal defect correction with 4D Flow cardiovascular magnetic resonance and retrospective valve tracking 
Background
To characterize and directly quantify regurgitant jets of left atrioventricular valve (LAVV) in patients with corrected atrioventricular septal defect (AVSD) by four-dimensional (4D)Flow Cardiovascular Magnetic Resonance (CMR), streamline visualization and retrospective valve tracking.
Methods
Medical ethical committee approval and informed consent from all patients or their parents were obtained. In 32 corrected AVSD patients (age 26 ± 12 years), echocardiography and whole-heart 4DFlow CMR were performed. Using streamline visualization on 2- and 4-chamber views, the angle between regurgitation and annulus was followed throughout systole. On through-plane velocity-encoded images reformatted perpendicular to the regurgitation jet the cross-sectional jet circularity index was assessed and regurgitant volume and fraction were calculated. Correlation and agreement between different techniques was performed with Pearson’s r and Spearman’s rho correlation and Bland-Altman analysis.
Results
In 8 patients, multiple regurgitant jets over the LAVV were identified. Median variation in regurgitant jet angle within patients was 36°(IQR 18–64°) on the 2-chamber and 30°(IQR 20–40°) on the 4-chamber. Regurgitant jets had a circularity index of 0.61 ± 0.16. Quantification of the regurgitation volume was feasible with 4DFlow CMR with excellent correlation between LAVV effective forward flow and aortic flow (r = 0.97, p < 0.001) for internal validation and moderate correlation with planimetry derived regurgitant volume (r = 0.65, p < 0.001) and echocardiographic grading (rho = 0.51, p = 0.003).
Conclusions
4DFlow CMR with streamline visualization revealed multiple, dynamic and eccentric regurgitant jets with non-circular cross-sectional shape in patients after AVSD correction. 4DFlow with retrospective valve tracking allows direct and accurate quantification of the regurgitation of these complex jets.
doi:10.1186/s12968-015-0122-4
PMCID: PMC4332442
4DFlow; Mitral valve regurgitation; Atrioventricular septal defect; Cardiovascular magnetic resonance
4.  Gender specific patterns of age-related decline in aortic stiffness: a cardiovascular magnetic resonance study including normal ranges 
Background
Young females exhibit lower cardiovascular event rates that young men, a pattern which is lost, or even reversed with advancing age. As aortic stiffness is a powerful risk factor for cardiovascular events, a gender difference with advancing age could provide a plausible explanation for this pattern.
Methods
777 subjects (♀n = 408, ♂n = 369) across a wide range of age (21–85 years) underwent cardiovascular magnetic resonance to assess aortic pulse wave velocity (PWV) and, in addition, aortic distensibility at three levels; 1) ascending aorta (Ao) and 2) proximal descending aorta (PDA) at the level of the pulmonary artery and 3) the abdominal aorta (DDA).
Results
There was a strong negative correlation between increasing age and regional aortic distensibility (Ao♀R-0.84, ♂R-0.80, PDA♀R-0.82, ♂R-0.77, DDA♀R-0.80, ♂R-0.71 all p < 0.001) and a strong positive correlation with PWV, (♀R0.53, ♂R 0.63 both p < 0.001). Even after adjustment for mean arterial pressure, body mass index, heart rate, smoking and diabetes, females exhibited a steeper decrease in all distensibility measures in response to increasing age (Ao♀-1.3 vs ♂-1.1 mmHg-1, PDA ♀-1.2 vs ♂-1.0 mmHg, DDA ♀-1.8 vs ♂-1.4 mmHg-1 per 10 years increase in age all p < 0.001). No gender difference in PWV increase with age was observed (p = 0.11).
Conclusion
Although advancing age is accompanied by increased aortic stiffness in both males and females, a significant sex difference in the rate of change exists, with females showing a steeper decline in aortic elasticity. As aortic stiffness is strongly related to cardiovascular events our observations may explain the increase in cardiovascular event rates that accompanies the menopausal age in women.
doi:10.1186/s12968-015-0126-0
PMCID: PMC4332729
Aorta; Cardiovascular magnetic resonance; Age
5.  Effects of age and smoking on endothelial function assessed by quantitative cardiovascular magnetic resonance in the peripheral and central vasculature 
Background
Both age and smoking promote endothelial dysfunction and impair vascular reactivity. Here, we tested this hypothesis by quantifying new cardiovascular magnetic resonance (CMR)-based biomarkers in smokers and nonsmokers.
Methods
Study population: young non-smokers (YNS: N = 45, mean age = 30.2 ± 0.7 years), young smokers (YS: N = 39 mean age 32.1 ± 0.7 years), older non-smokers (ONS: N = 45, mean age = 57.8 ± 0.6 years), and older smokers (OS: N = 40, mean age = 56.3 ± 0.6 years), all without overt cardiovascular disease. Vascular reactivity was evaluated following cuff-induced hyperemia via time-resolved blood flow velocity and oxygenation (SvO2) in the femoral artery and vein, respectively. SvO2 dynamics yielded washout time (time to minimum SvO2), resaturation rate (upslope) and maximum change from baseline (overshoot). Arterial parameters included pulse ratio (PR), hyperemic index (HI) and duration of hyperemia (TFF). Pulse-wave velocity (PWV) was assessed in aortic arch, thoracoabdominal aorta and iliofemoral arteries. Ultrasound-based carotid intimal-medial thickness (IMT) and brachial flow-mediated dilation were measured for comparison.
Results
Age and smoking status were independent for all parameters. Smokers had reduced upslope (−28.4%, P < 0.001), increased washout time (+15.3%, P < 0.01), and reduced HI (−19.5%, P < 0.01). Among non-smokers, older subjects had lower upslope (−22.7%, P < 0.01) and overshoot (−29.4%, P < 0.01), elevated baseline pulse ratio (+14.9%, P < 0.01), central and peripheral PWV (all P < 0.05). Relative to YNS, YS had lower upslope (−23.6%, P < 0.01) and longer washout time (13.5%, P < 0.05). Relative to ONS, OS had lower upslope (−33.0%, P < 0.01). IMT was greater in ONS than in YNS (+45.6%, P < 0.001), and also in YS compared to YNS (+14.7%, P < 0.05).
Conclusions
Results suggest CMR biomarkers of endothelial function to be sensitive to age and smoking independent of each other.
doi:10.1186/s12968-015-0110-8
PMCID: PMC4332734
Vascular reactivity; Oximetry; Velocimetry; Pulse wave velocity; Smoking; Aging; Cardiovascular magnetic resonance
6.  Optimization of dual-saturation single bolus acquisition for quantitative cardiac perfusion and myocardial blood flow maps 
Background
In-vivo quantification of cardiac perfusion is of great research and clinical value. The dual-bolus strategy is universally used in clinical protocols but has known limitations. The dual-saturation acquisition strategy has been proposed as a more accurate alternative, but has not been validated across the wide range of perfusion rates encountered clinically. Dual-saturation acquisition also lacks a clinically-applicable procedure for optimizing parameter selection. Here we present a comprehensive validation study of dual-saturation strategy in vitro and in vivo.
Methods
The impact of saturation time and profile ordering in acquisitions was systematically analyzed in a phantom consisting of 15 tubes containing different concentrations of contrast agent. In-vivo experiments in healthy pigs were conducted to evaluate the effect of R2* on the definition of the arterial input function (AIF) and to evaluate the relationship between R2* and R1 variations during first-pass of the contrast agent. Quantification by dual-saturation perfusion was compared with the reference-standard dual-bolus strategy in 11 pigs with different grades of myocardial perfusion.
Results
Adequate flow estimation by the dual-saturation strategy is achieved with myocardial tissue saturation times around 100 ms (always <30 ms of AIF), with the lowest echo time, and following a signal model for contrast conversion that takes into account the residual R2* effect and profile ordering. There was a good correlation and agreement between myocardial perfusion quantitation by dual-saturation and dual-bolus techniques (R2 = 0.92, mean difference of 0.1 ml/min/g; myocardial perfusion ranges between 0.18 and 3.93 ml/min/g).
Conclusions
The dual-saturation acquisition strategy produces accurate estimates of absolute myocardial perfusion in vivo. The procedure presented here can be applied with minimal interference in standard clinical procedures.
doi:10.1186/s12968-015-0116-2
PMCID: PMC4332925
Dual saturation acquisition strategy; Absolute quantitative cardiac perfusion; Cardiovascular magnetic resonance
7.  FLASH proton density imaging for improved surface coil intensity correction in quantitative and semi-quantitative SSFP perfusion cardiovascular magnetic resonance 
Background
A low excitation flip angle (α < 10°) steady-state free precession (SSFP) proton-density (PD) reference scan is often used to estimate the B1-field inhomogeneity for surface coil intensity correction (SCIC) of the saturation-recovery (SR) prepared high flip angle (α = 40-50°) SSFP myocardial perfusion images. The different SSFP off-resonance response for these two flip angles might lead to suboptimal SCIC when there is a spatial variation in the background B0-field. The low flip angle SSFP-PD frames are more prone to parallel imaging banding artifacts in the presence of off-resonance. The use of FLASH-PD frames would eliminate both the banding artifacts and the uneven frequency response in the presence of off-resonance in the surface coil inhomogeneity estimate and improve homogeneity of semi-quantitative and quantitative perfusion measurements.
Methods
B0-field maps, SSFP and FLASH-PD frames were acquired in 10 healthy volunteers to analyze the SSFP off-resonance response. Furthermore, perfusion scans preceded by both FLASH and SSFP-PD frames from 10 patients with no myocardial infarction were analyzed semi-quantitatively and quantitatively (rest n = 10 and stress n = 1). Intra-subject myocardial blood flow (MBF) coefficient of variation (CoV) over the whole left ventricle (LV), as well as intra-subject peak contrast (CE) and upslope (SLP) standard deviation (SD) over 6 LV sectors were investigated.
Results
In the 6 out of 10 cases where artifacts were apparent in the LV ROI of the SSFP-PD images, all three variability metrics were statistically significantly lower when using the FLASH-PD frames as input for the SCIC (CoVMBF-FLASH = 0.3 ± 0.1, CoVMBF-SSFP = 0.4 ± 0.1, p = 0.03; SDCE-FLASH = 10 ± 2, SDCE-SSFP = 32 ± 7, p = 0.01; SDSLP-FLASH = 0.02 ± 0.01, SDSLP-SSFP = 0.06 ± 0.02, p = 0.03). Example rest and stress data sets from the patient pool demonstrate that the low flip angle SSFP protocol can exhibit severe ghosting artifacts originating from off-resonance banding artifacts at the edges of the field of view that parallel imaging is not able to unfold. These artifacts lead to errors in the quantitative perfusion maps and the semi-quantitative perfusion indexes, such as false positives. It is shown that this can be avoided by using FLASH-PD frames as input for the SCIC.
Conclusions
FLASH-PD images are recommended as input for SCIC of SSFP perfusion images instead of low flip angle SSFP-PD images.
doi:10.1186/s12968-015-0120-6
PMCID: PMC4331176
Myocardial perfusion; Quantitative perfusion; Cardiovascular magnetic resonance; Surface coil correction; Proton density frames; Balanced Steady State Free Precession (SSFP); Fast Low Angle SHot (FLASH)
8.  Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus 
Background
Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods.
Methods
Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05.
Results
Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling.
Conclusions
Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-015-0125-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12968-015-0125-1
PMCID: PMC4331385
Cardiovascular magnetic resonance; Myocardial blood flow; Fermi modeling; Distributed parameter modeling; Fractional flow reserve; Invasive coronary angiography
9.  Quantification of myocardial perfusion with self-gated cardiovascular magnetic resonance 
Background
Current myocardial perfusion measurements make use of an ECG-gated pulse sequence to track the uptake and washout of a gadolinium-based contrast agent. The use of a gated acquisition is a problem in situations with a poor ECG signal. Recently, an ungated perfusion acquisition was proposed but it is not known how accurately quantitative perfusion estimates can be made from such datasets that are acquired without any triggering signal.
Methods
An undersampled saturation recovery radial turboFLASH pulse sequence was used in 7 subjects to acquire dynamic contrast-enhanced images during free-breathing. A single saturation pulse was followed by acquisition of 4–5 slices after a delay of ~40 msec. This was repeated without pause and without any type of gating. The same pulse sequence, with ECG-gating, was used to acquire gated data as a ground truth. An iterative spatio-temporal constrained reconstruction was used to reconstruct the undersampled images. After reconstruction, the ungated images were retrospectively binned (“self-gated”) into two cardiac phases using a region of interest based technique and deformably registered into near-systole and near-diastole. The gated and the self-gated datasets were then quantified with standard methods.
Results
Regional myocardial blood flow estimates (MBFs) obtained using self-gated systole (0.64 ± 0.26 ml/min/g), self-gated diastole (0.64 ± 0.26 ml/min/g), and ECG-gated scans (0.65 ± 0.28 ml/min/g) were similar. Based on the criteria for interchangeable methods listed in the statistical analysis section, the MBF values estimated from self-gated and gated methods were not significantly different.
Conclusion
The self-gated technique for quantification of regional myocardial perfusion matched ECG-gated perfusion measurements well in normal subjects at rest. Self-gated systolic perfusion values matched ECG-gated perfusion values better than did diastolic values.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-015-0109-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12968-015-0109-1
PMCID: PMC4325943
Cardiovascular magnetic resonance; Myocardial perfusion; Quantitative perfusion; ECG-gating; Self-gated
10.  Feasibility of high-resolution quantitative perfusion analysis in patients with heart failure 
Background
Cardiac magnetic resonance (CMR) is playing an expanding role in the assessment of patients with heart failure (HF). The assessment of myocardial perfusion status in HF can be challenging due to left ventricular (LV) remodelling and wall thinning, coexistent scar and respiratory artefacts. The aim of this study was to assess the feasibility of quantitative CMR myocardial perfusion analysis in patients with HF.
Methods
A group of 58 patients with heart failure (HF; left ventricular ejection fraction, LVEF ≤ 50%) and 33 patients with normal LVEF (LVEF >50%), referred for suspected coronary artery disease, were studied. All subjects underwent quantitative first-pass stress perfusion imaging using adenosine according to standard acquisition protocols. The feasibility of quantitative perfusion analysis was then assessed using high-resolution, 3 T kt perfusion and voxel-wise Fermi deconvolution.
Results
30/58 (52%) subjects in the HF group had underlying ischaemic aetiology. Perfusion abnormalities were seen amongst patients with ischaemic HF and patients with normal LV function. No regional perfusion defect was observed in the non-ischaemic HF group. Good agreement was found between visual and quantitative analysis across all groups. Absolute stress perfusion rate, myocardial perfusion reserve (MPR) and endocardial-epicardial MPR ratio identified areas with abnormal perfusion in the ischaemic HF group (p = 0.02; p = 0.04; p = 0.02, respectively). In the Normal LV group, MPR and endocardial-epicardial MPR ratio were able to distinguish between normal and abnormal segments (p = 0.04; p = 0.02 respectively). No significant differences of absolute stress perfusion rate or MPR were observed comparing visually normal segments amongst groups.
Conclusions
Our results demonstrate the feasibility of high-resolution voxel-wise perfusion assessment in patients with HF.
doi:10.1186/s12968-015-0124-2
PMCID: PMC4326191
Heart failure; Quantitative perfusion; Cardiovascular magnetic resonance; Gadolinium
11.  Gradient Spin Echo (GraSE) imaging for fast myocardial T2 mapping 
Background
Quantitative Cardiovascular Magnetic Resonance (CMR) techniques have gained high interest in CMR research. Myocardial T2 mapping is thought to be helpful in diagnosis of acute myocardial conditions associated with myocardial edema. In this study we aimed to establish a technique for myocardial T2 mapping based on gradient-spin-echo (GraSE) imaging.
Methods
The local ethics committee approved this prospective study. Written informed consent was obtained from all subjects prior to CMR. A modified GraSE sequence allowing for myocardial T2 mapping in a single breath-hold per slice using ECG-triggered acquisition of a black blood multi-echo series was developed at 1.5 Tesla. Myocardial T2 relaxation time (T2-RT) was determined by maximum likelihood estimation from magnitude phased-array multi-echo data. Four GraSE sequence variants with varying number of acquired echoes and resolution were evaluated in-vitro and in 20 healthy volunteers. Inter-study reproducibility was assessed in a subset of five volunteers. The sequence with the best overall performance was further evaluated by assessment of intra- and inter-observer agreement in all volunteers, and then implemented into the clinical CMR protocol of five patients with acute myocardial injury (myocarditis, takotsubo cardiomyopathy and myocardial infarction).
Results
In-vitro studies revealed the need for well defined sequence settings to obtain accurate T2-RT measurements with GraSE. An optimized 6-echo GraSE sequence yielded an excellent agreement with the gold standard Carr-Purcell-Meiboom-Gill sequence. Global myocardial T2 relaxation times in healthy volunteers was 52.2 ± 2.0 ms (mean ± standard deviation). Mean difference between repeated examinations (n = 5) was −0.02 ms with 95% limits of agreement (LoA) of [−4.7; 4.7] ms. Intra-reader and inter-reader agreement was excellent with mean differences of −0.1 ms, 95% LoA = [−1.3; 1.2] ms and 0.1 ms, 95% LoA = [−1.5; 1.6] ms, respectively (n = 20). In patients with acute myocardial injury global myocardial T2-RTs were prolonged (mean: 61.3 ± 6.7 ms).
Conclusion
Using an optimized GraSE sequence CMR allows for robust, reliable, fast myocardial T2 mapping and quantitative tissue characterization. Clinically, the GraSE-based T2-mapping has the potential to complement qualitative CMR in patients with acute myocardial injuries.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-015-0127-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12968-015-0127-z
PMCID: PMC4326516
Cardiovascular magnetic resonance; T2 mapping; Phantom study; Quantitative MRI; Gradient-spin-echo imaging
12.  The association between cardiovascular risk and cardiovascular magnetic resonance measures of fibrosis: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Risk scores for cardiovascular disease (CVD) are in common use to integrate multiple cardiovascular risk factors in order to identify individuals at greatest risk for disease. The purpose of this study was to determine if individuals at greater cardiovascular risk have T1 mapping indices by cardiovascular magnetic resonance (CMR) indicative of greater myocardial fibrosis.
Methods
CVD risk scores for 1208 subjects (men, 50.8%) ages 55–94 years old were evaluated in the Multiethnic Study of Atherosclerosis (MESA) at six centers. T1 times were determined at 1.5Tesla before and after gadolinium administration (0.15 mmol/kg) using a modified Look-Locker pulse sequence. The relationship between CMR measures (native T1, 12 and 25 minute post-gadolinium T1, partition coefficient and extracellular volume fraction) and 14 established different cardiovascular risk scores were determined using regression analysis. Bootstrapping analysis with analysis of variance was used to compare different CMR measures. CVD risk scores were significantly different for men and women (p < 0.001).
Results
25 minute post gadolinium T1 time showed more statistically significant associations with risk scores (10/14 scores, 71%) compared to other CMR indices (e.g. native T1 (7/14 scores, 50%) and partition coefficient (7/14, 50%) in men. Risk scores, particularly the new 2013 AHA/ASCVD risk score, did not correlate with any CMR fibrosis index.
Conclusions
Men with greater CVD risk had greater CMR indices of myocardial fibrosis. T1 times at greater delay time (25 minutes) showed better agreement with commonly used risk score indices compared to ECV and native T1 time.
Clinical trial registration
http://www.mesa-nhlbi.org/, NCT00005487.
doi:10.1186/s12968-015-0121-5
PMCID: PMC4326517
Myocardium; Cardiovascular magnetic resonance; Risk factors
13.  Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease 
Background
Cardiovascular magnetic resonance (CMR) provides non-invasive and more accurate assessment of right ventricular (RV) function in comparison to echocardiography. Recent study demonstrated that assessment of RV function by echocardiography was an independent predictor for mortality in patients with interstitial lung disease (ILD). The purpose of this study was to determine the prognostic significance of CMR derived RV ejection fraction (RVEF) in ILD patients.
Methods
We enrolled 76 patients with ILD and 24 controls in the current study. By using 1.5 T CMR scanner equipped with 32 channel cardiac coils, we performed steady-state free precession cine CMR to assess the RVEF. RV systolic dysfunction (RVSD) was defined as RVEF ≤45.0% calculated by long axis slices. Pulmonary hypertension (PH) was defined as mean pulmonary artery pressure (mPAP) of more than 25 mmHg at rest in the setting of pulmonary capillary wedge pressure ≤15 mmHg.
Results
The median RVEF was 59.2% in controls (n = 24), 53.8% in ILD patients without PH (n = 42) and 43.1% in ILD patients with PH (n = 13) (p < 0.001 by one-way ANOVA). During a mean follow-up of 386 days, 18 patients with RVSD had 11 severe events (3 deaths, 3 right heart failure, 3 exacerbation of dyspnea requiring oxygen, 2 pneumonia requiring hospitalization). In contrast, only 2 exacerbation of dyspnea requiring oxygen were observed in 58 patients without RVSD. Multivariate Cox regression analysis showed that RVEF independently predicted future events, after adjusting for age, sex and RVFAC by echocardiography (hazard ratio: 0.889, 95% confidence interval: 0.809 – 0.976, p = 0.014).
Conclusions
The current study demonstrated that RVSD in ILD patients can be clearly detected by cine CMR. Importantly, low prevalence of PH (17%) indicated that population included many mild ILD patients. CMR derived RVEF might be useful for the risk stratification and clinical management of ILD patients.
doi:10.1186/s12968-015-0113-5
PMCID: PMC4323037
Interstitial lung disease; Magnetic resonance imaging; Right ventricular function
14.  Quantitative pixel-wise measurement of myocardial blood flow: The impact of surface coil-related field inhomogeneity and a comparison of methods for its correction 
Background
Surface coil-related field inhomogeneity potentially confounds pixel-wise quantitative analysis of perfusion CMR images. This study assessed the effect of surface coil-related field inhomogeneity on the spatial variation of pixel-wise myocardial blood flow (MBF), and assessed its impact on the ability of MBF quantification to differentiate ischaemic from remote coronary territories. Two surface coil intensity correction (SCIC) techniques were evaluated: 1) a proton density-based technique (PD-SCIC) and; 2) a saturation recovery steady-state free precession-based technique (SSFP-SCIC).
Methods
26 subjects (18 with significant CAD and 8 healthy volunteers) underwent stress perfusion CMR using a motion-corrected, saturation recovery SSFP dual-sequence protocol. A proton density (PD)-weighted image was acquired at the beginning of the sequence. Surface coil-related field inhomogeneity was approximated using a third-order surface fit to the PD image or a pre-contrast saturation prepared SSFP image. The estimated intensity bias field was subsequently applied to the image series. Pixel-wise MBF was measured from mid-ventricular stress images using the two SCIC approaches and compared to measurements made without SCIC.
Results
MBF heterogeneity in healthy volunteers was higher using SSFP-SCIC (24.8 ± 4.1%) compared to PD-SCIC (20.8 ± 3.0%; p = 0.009), however heterogeneity was significantly lower using either SCIC technique compared to analysis performed without SCIC (36.2 ± 6.3%). In CAD patients, the difference in MBF between remote and ischaemic territories was minimal when analysis was performed without SCIC (0.06 ± 0.91 mL/min/kg), and was substantially lower than with either PD-SCIC (0.50 ± 0.63 mL/min/kg; p = 0.013) or with SSFP-SCIC (0.63 ± 0.89 mL/min/kg; p = 0.005). In 6 patients, MBF quantified without SCIC was artifactually higher in the stenosed coronary territory compared to the remote territory. PD-SCIC and SSFP-SCIC had similar differences in MBF between remote and ischaemic territories (p = 0.145).
Conclusions
This study demonstrates that surface coil-related field inhomogeneity can confound pixel-wise MBF quantification. Whilst a PD-based SCIC led to a more homogenous correction than a saturation recovery SSFP-based technique, this did not result in an appreciable difference in the differentiation of ischaemic from remote coronary territories and thus either method could be applied.
doi:10.1186/s12968-015-0117-1
PMCID: PMC4323126
Cardiovascular magnetic resonance; Perfusion; Myocardial blood flow; Quantification; Field inhomogeneity; Surface coil intensity correction
15.  Myocardial T2 mapping reveals age- and sex-related differences in volunteers 
Background
T2 mapping indicates to be a sensitive method for detection of tissue oedema hidden beyond the detection limits of T2-weighted Cardiovascular Magnetic Resonance (CMR). However, due to variability of baseline T2 values in volunteers, reference values need to be defined. Therefore, the aim of the study was to investigate the effects of age and sex on quantitative T2 mapping with a turbo gradient-spin-echo (GRASE) sequence at 1.5 T. For that reason, we studied sensitivity issues as well as technical and biological effects on GRASE-derived myocardial T2 maps. Furthermore, intra- and interobserver variability were calculated using data from a large volunteer group.
Methods
GRASE-derived multiecho images were analysed using dedicated software. After sequence optimization, validation and sensitivity measurements were performed in muscle phantoms ex vivo and in vivo. The optimized parameters were used to analyse CMR images of 74 volunteers of mixed sex and a wide range of age with typical prevalence of hypertension and diabetes. Myocardial T2 values were analysed globally and according to the 17 segment model. Strain-encoded (SENC) imaging was additionally performed to investigate possible effects of myocardial strain on global or segmental T2 values.
Results
Ex vivo studies in muscle phantoms showed, that GRASE-derived T2 values were comparable to those acquired by a standard multiecho spinecho sequence but faster by a factor of 6. Besides that, T2 values reflected tissue water content. The in vivo measurements in volunteers revealed intra- and interobserver correlations with R2=0.91 and R2=0.94 as well as a coefficients of variation of 2.4% and 2.2%, respectively. While global T2 time significantly decreased towards the heart basis, female volunteers had significant higher T2 time irrespective of myocardial region. We found no correlation of segmental T2 values with maximal systolic, diastolic strain or heart rate. Interestingly, volunteers´ age was significantly correlated to T2 time while that was not the case for other coincident cardiovascular risk factors.
Conclusion
GRASE-derived T2 maps are highly reproducible. However, female sex and aging with typical prevalence of hypertension and diabetes were accompanied by increased myocardial T2 values. Thus, sex and age must be considered as influence factors when using GRASE in a diagnostic manner.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-015-0118-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12968-015-0118-0
PMCID: PMC4318191  PMID: 25656484
Cardiovascular magnetic resonance; T2 mapping; Volunteer study; SENC
16.  Myocardial T2* mapping: influence of noise on accuracy and precision 
Background
Pixel-wise, parametric T2* mapping is emerging as a means of automatic measurement of iron content in tissues. It enables quick, intuitive interpretation and provides the potential benefit of spatial context between tissues. However, pixel-wise mapping uses much lower SNR data to estimate T2* when compared to region-based mapping thereby decreasing both its accuracy and precision. In this study, the effects that noise has on the precision and accuracy of pixel-wise T2* mapping were investigated and techniques to mitigate those effects are proposed.
Methods
To study precision across T2* mapping techniques, a pipeline to estimate the pixel-wise standard deviation (SD) of the T2* based on the fit residuals is proposed. For validation, a Monte-Carlo analysis was performed in which T2* phantoms were scanned N = 64 times, the true SD was measured and compared to the estimated SD. To improve accuracy and precision, the automatic truncation method for mitigating noise bias was extended to pixel-wise fitting by using an SNR scaled image reconstruction and truncating low SNR measurements. Finally, the precision and accuracy of non-linear regression with and without automatic truncation, were investigated using Monte-Carlo simulations.
Results
Measured and estimated SD’s were >99.9% correlated for non-linear regression with and without truncation. Non-linear regression with automatic truncation was shown to be the best mapping technique for improving accuracy and precision in low T2* and low SNR measurements.
Conclusions
A method for applying an automatic truncation method to pixel-wise T2* mapping that reduces T2* overestimation due to noise bias was proposed. A formulation for estimating pixel-wise standard deviation (SD) maps for T2* that can serve as a quality map for interpreting images and for comparison of imaging protocols was also proposed and validated.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-015-0115-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12968-015-0115-3
PMCID: PMC4316604  PMID: 25648167
T2* mapping; Iron overload; Mapping; Hemochromatosis; Thalassemia
17.  Inter-study reproducibility of interleaved spiral phase velocity mapping of renal artery haemodynamics 
Background
Qualitative and quantitative assessment of renal blood flow is valuable in the evaluation of patients with renal and renovascular diseases as well as in patients with heart failure. The temporal pattern of renal flow velocity through the cardiac cycle provides important information about renal haemodynamics. High temporal resolution interleaved spiral phase velocity mapping could potentially be used to study temporal patterns of flow and measure resistive and pulsatility indices which are measures of downstream resistance.
Methods
A retrospectively gated breath-hold spiral phase velocity mapping sequence (TR 19 ms) was developed at 3 Tesla. Phase velocity maps were acquired in the proximal right and left arteries of 10 healthy subjects in each of two separate scanning sessions. Each acquisition was analysed by two independent observers who calculated the resistive index (RI), the pulsatility index (PI), the mean flow velocity and the renal artery blood flow (RABF). Inter-study and inter-observer reproducibility of each variable was determined as the mean +/− standard deviation of the differences between paired values. The effect of background phase errors on each parameter was investigated.
Results
RI, PI, mean velocity and RABF per kidney were 0.71+/− 0.06, 1.47 +/− 0.29, 253.5 +/− 65.2 mm/s and 413 +/− 122 ml/min respectively. The inter-study reproducibilities were: RI −0.00 +/− 0.04 , PI −0.03 +/− 0.17, mean velocity −6.7 +/− 31.1 mm/s and RABF per kidney 17.9 +/− 44.8 ml/min. The effect of background phase errors was negligible (<2% for each parameter).
Conclusions
High temporal resolution breath-hold spiral phase velocity mapping allows reproducible assessment of renal pulsatility indices and RABF.
doi:10.1186/s12968-014-0105-x
PMCID: PMC4316806  PMID: 25648103
Spiral; Phase velocity mapping; Renal blood flow; Resistive index; Pulsatility index; Reproducibility

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